This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kleuser, B. Articles by Adam, G. Search for Related Content PubMed PubMed Citation Articles by Kleuser, B. Articles by Adam, G.

Selective Effects by Valinomycin on Cytotoxicity and Cell Cycle Arrest of Transformed versus Nontransformed Rodent Fibroblasts in Vitro¹

Fakultät für Biologie, Universität Konstanz, D-7750 Konstanz, Federal Republic of Germany

The effect of submicromolar concentrations of the K⁺ ionophore valinomycin on proliferation, viability, distribution of cell population over phases of the cell cycle, and cellular adenosine triphosphate content of different permanent rodent cell lines in vitro was investigated. Valinomycin inhibits proliferation of all cell lines tested with a saturating effect at about 20 to 100 nM. The effect of valinomycin on nontransformed 3T3 mouse and Rat-1 cells is nontoxic, whereas it acts with increasing toxicity on the transformed cells in the order 3T6 mouse, polyoma-3T3 mouse, temperature-sensitively Rous sarcoma virus-transformed Rat-1 at permissive temperature, and SV40-3T3 cells. According to these and some other criteria, the essential action of valinomycin appears to be to impose on the cells at low growth densities a state of limiting growth condition which normally is encountered only at high cell densities and/or low serum concentration.

Nontransformed cells are proliferation arrested by valinomycin essentially in the G₁ phase of the cell cycle, whereas all transformed cells under this condition are not arrested selectively in G₁. In all cell lines tested (3T3, 3T6, and SV40-3T3), cellular adenosine triphosphate content is decreased by about 33% upon treatment with 20 nM valinomycin. Evidence is presented for a mitochondrial site of action of valinomycin.

¹ Supported by grants from Stiftung Volkswagenwerk (Schwerpunkt Synergetik) and Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 156).

² To whom requests for reprints should be addressed.

Received 12/26/84. Revised 3/18/85. Accepted 4/ 4/85.